Good day, welcome to Jazz Pharmaceuticals fourth quarter and full year 2022 financial results call. At this time, all participants are in listen only mode. After the speaker's presentation, there'll be a question and answer session. Instructions will be given at that time. As a reminder, this call is being recorded. I would now like to turn the call over to Darren Fox, Executive Director of Investor Relations. You may begin. Thank you, operator, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its fourth quarter and full year 2022 financial results. The slide presentation accompanying this webcast is available on the investors section of our website. Investors may also refer to the press release we issued earlier today, which is also posted on our website. On the call today are Bruce Cozadd, Chairman and Chief Executive Officer, Renée Galá, Executive Vice President and Chief Financial Officer, Dan Swisher, President and Chief Operating Officer, and Robert Iannone, Executive Vice President, Global Head of R&D. Kim Sablich, Executive Vice President and General Manager, United States, will join the team for Q&A. On slide two, I'd like to remind you that today's webcast includes forward-looking statements, such as those related to our future financial and operating results, growth potential, and anticipated development and commercialization milestones and goals, which involve risks and uncertainties that could cause actual events, performance and results to differ materially from those contained in these forward-looking statements. We encourage you to review the statements contained in today's press release, in our slide deck, and in our latest SEC disclosure document, which identifies certain factors that may cause the company's actual events, performance and results to differ materially from those contained in the forward-looking statements made on today's webcast. We undertake no duty or obligation to update our forward-looking statements. Turning to slide three. On this webcast, we'll discuss non-GAAP financial measures. Reconciliations of GAAP to non-GAAP financial measures are included in today's press release and the slide presentation available on the investors section of our website. I'll now turn the call over to Bruce. Thanks, Darren. Good afternoon, everyone, and thank you for joining us today. I'm excited to share our strong fourth quarter and full year results, capping off an outstanding year of performance and execution for Jazz, providing us with significant momentum as we enter 2023 and continue to drive toward Vision 2025. I'll start on slide five. This year, Jazz is celebrating its 20th anniversary. Over those 20 years, we've remained focused on our purpose of improving the lives of patients and our commitment to being a great place to work while delivering consistent top-line growth. In 2022, we built on that foundation of strong execution, achieving record revenue, advancing multiple therapies in our pipeline, and adding several exciting molecules through corporate development, all while remaining focused on disciplined capital allocation and operational excellence. All of these accomplishments contributed to the ongoing transformation of our business to a high-growth global biopharma leader and position us well to achieve Vision 2025. Vision 2025 includes three components central to driving sustainable growth and enhanced value as we transform our company, commercial, pipeline, and operational excellence. I'll now highlight several of our accomplishments in each of those areas in 2022, starting with commercial. Based on our strong commercial performance, we continue to deliver significant revenue growth. In 2022, we recorded $3.7 billion in revenue, which represented an 18% increase compared to 2021. Our top-line growth was driven by the continued success of three recently launched products, Xywav, Zepzelca, and Rylaze, along with strong growth for Epidiolex. Xywav is now our largest product by revenue, annualizing at more than $1 billion. Based on our outstanding commercial execution, we achieved our 2022 total revenue guidance as well as guidance for each of our neuroscience and oncology franchises. Moving to the pipeline, we continued to advance our clinical portfolio and added three exciting new molecules to our pipeline during 2022. Within the past three months, our most recent oncology pipeline addition, zanidatamab, has had positive data readouts in both of its initial target indications. Over the course of the year, we initiated seven new clinical trials, submitted four new INDs, generated multiple important data sets, and received regulatory approval for an important update to Rylaze dosing. Our pipeline has never been as robust or productive as it is right now, and we have multiple value inflection points over the next 12 to 24 months. On operational excellence, our continued focus on disciplined capital allocation and operating efficiency drove a 2022 adjusted operating margin of 48%, which represents a substantial increase from the 43% we recorded in 2021. We significantly reduced our net leverage ratio and continued to diversify our revenues in 2022, while also executing multiple strategic transactions that we believe will create sustainable value for patients and shareholders. These achievements on both the top and bottom line enabled us to significantly increase our operating cash flow and financial strength. We generated $1.3 billion in cash from operations, the overall health of our balance sheet is enabling us to be active in pursuing additional corporate development opportunities. Turning to slide six, we've made substantial progress since introducing Vision 2025 last January, we remain focused on our transformation to a high-growth global biopharma leader. Our many accomplishments in 2022 have positioned us well for 2023. Despite the recent introduction of an authorized generic of Xyrem, which until recently was the company's largest product by net sales, we are entering the year with an expectation of achieving top-line revenue growth in 2023 and remain confident in our ability to achieve the important milestones underpinning Vision 2025. I'll now turn the call over to Dan for an overview of our commercial performance. After which Rob will share an update on progress across our R&D programs. Renée will provide a financial overview, which will include a discussion of our 2023 guidance in addition to 2022 performance. We'll open the call to Q&A. Dan? Thanks, Bruce. I'm excited to share the continued progress across our commercial portfolio. I'll start on slide 8 with neuroscience and oxybate. As a leader in sleep medicine, we believe the approval of Xywav in mid-2020 marked a meaningful advance in patient care. As a lower sodium oxybate, Xywav has offered patients with narcolepsy and IH who are taking a lifelong therapy to address their sleep disorders, a way to reduce sodium intake, which is a known risk factor for cardiovascular disease. In the fourth quarter, average active oxybate patients increased to approximately 18,000, representing growth of approximately 11% compared to the same period last year. There were approximately 10,300 active Xywav patients exiting the quarter, resulting from strong adoption in both narcolepsy and IH. Over the course of 2022, this compelling adoption continued to reinforce our confidence in the durability of Xywav, and we expect Xywav to grow and remain the oxybate of choice in 2023. As Bruce noted, Xywav became our largest product in net sales in fourth quarter 2022, annualizing at more than $1 billion and on track to achieve blockbuster status in 2023. We continued to see robust uptake of Xywav for narcolepsy in the fourth quarter, and we exited the quarter with approximately 8,550 narcolepsy patients taking Xywav. There are now more narcolepsy patients on Xywav than Xyrem, indicating our sodium messaging is resonating with healthcare providers and patients. In addition to adoption of Xywav among current Xyrem patients, the large majority of new to oxybate narcolepsy patients are being prescribed Xywav. Xywav is the first and only FDA-approved therapy for IH, and we are continuing to see increased enthusiasm among physicians for identifying appropriate patients and initiating therapy. Exiting the fourth quarter, there were approximately 1,750 IH patients taking Xywav. We remain focused on educating prescribers and patients about the compelling efficacy and established safety profile of Xywav, and are confident in our ability to maximize Xywav's potential in this underserved market. I also wanna comment on the evolving landscape for oxybate. In January 2023, an authorized generic of Xyrem was launched. We expect that Xywav will both grow and remain the oxybate of choice in 2023, even with one or more authorized generics on the market and branded competition potentially entering the marketplace this year. Xywav remains the only lower sodium oxybate available to patients. We expect it to be the only oxybate indicated for IH for the foreseeable future. FDA has recognized Xywav as clinically superior to Xyrem by means of greater safety. We have orphan drug exclusivity that extends to 2027 for narcolepsy and 2028 for IH, as well as Orange Book listed patents that extend out to 2033. All of these factors give us confidence that Xywav is a durable product that will continue to be a core growth driver for Jazz. Turning to slide nine, in Epidiolex, net product sales grew by 7% in the fourth quarter and 12% for the full year 2022 compared to same periods in 2021 on a pro forma basis, with growth driven primarily by underlying demand. Now that we are several years out from launch, we have visibility into seasonality trends. Inventory typically builds over the course of the second half of the year, which results in lower revenues in the first half. Our success in growing Epidiolex this year has been driven by a number of factors, including increased access to treatment centers and physician offices, leading to more face-to-face interactions. Given the promotionally sensitive nature of Epidiolex and the anti-epilepsy market as a whole, greater access to HCPs has been a key driver. We continue to add new prescribers. Our volume of engagement with HCPs is increasing, and our market research indicates nearly 60% of prescribers are moving Epidiolex up in the treatment algorithm, all positive indicators for continued growth. There has been continued adoption of Epidiolex in ex-US markets. With the recent launch in France, Epidiolex is fully reimbursed and commercially available in all five major European markets. We remain excited about the future growth and blockbuster potential of Epidiolex. We are confident that with its unique mechanism of action and ability to be combined with other therapies, along with increasing positive experiences in real-world settings, Epidiolex can become a standard of care in treatment-resistant epilepsies and achieve blockbuster status. Now moving to slide 10 in Zepzelca. We have rapidly established Zepzelca as the treatment of choice in second-line small cell lung cancer, achieving $607 million in revenue since launch in mid-2020. Year-over-year revenue growth was 11% and 9% for the fourth quarter and full year respectively. We have multiple ongoing efforts to further expand market share in the second-line setting by investing in real-world evidence and observational studies that we believe will generate additional data around Zepzelca's utility in a broad range of second-line small cell lung cancer patients. Our robust development program, which Rob will outline in more detail shortly, is exploring the utility of Zepzelca in several new patient populations. Our nearest term opportunity for meaningful growth comes from the potential of Zepzelca to be used in first-line treatment of small cell lung cancer. We also have trials assessing the efficacy and safety of Zepzelca in other tumor types. As highlighted on slide 11, the Rylaze launch has been incredibly successful with $367 million in revenue since launch in mid-2021, including 25% revenue growth in the fourth quarter of 2022 compared to the same period in 2021. Rylaze remains the only therapy available to patients in the U.S. who have a hypersensitivity reaction to E. coli-derived asparaginase. It has been adopted universally in pediatric oncology protocols and having solved for the supply constraints for non-E. coli-derived asparaginase, healthcare professionals are reporting that they are returning to best clinical practice and switching ALL and LBL patients to Rylaze earlier when there has been an initial hypersensitivity reaction observed. We are encouraged to see that there is increasing use of Rylaze in the treatment of adolescents and young adults, a potential growth driver for 2023. To summarize, we are continuing to execute incredibly well on commercial and are maintaining the momentum to successful launches for our key products. I will turn the call over to Rob for an update on our pipeline progress in 2022 and milestones for 2023. Rob? Thanks, Dan. In recent years, we've enhanced the breadth and depth of our pipeline, as well as our R&D capabilities. Our acquisition of GW in 2021 accelerated that process. In 2022, we added three promising candidates to our pipeline. zanidatamab, a novel late-stage oncology asset, JZP441, an orexin-2 receptor agonist, for which we initiated a phase I clinical program in 2022, and JZP898, a differentiated, conditionally activated interferon alpha INDUKINE molecule that will be entering the clinic later this year. Starting on slide 13, I'll highlight the most recent addition to our pipeline, zanidatamab, a novel HER2-targeted bispecific antibody with biparatopic binding and the potential to transform the current standard of care in multiple HER2-expressing cancers. As an oncologist, I'm impressed to see monotherapy activity with zanidatamab across multiple HER2-expressing tumor types, including cases resistant to prior HER2 therapies. Based on its potential to benefit patients across multiple tumor types, we are committed to advancing this program as rapidly as possible. The most advanced clinical work with zanidatamab is in biliary tract cancers, or BTC, and metastatic gastroesophageal adenocarcinoma, or GEA. These are cancers with significant unmet need and poor outcomes with current standards of care. Our confidence in zanidatamab has only grown based on positive data in both of these settings. Continuing on to slide 14. We are very encouraged by the positive top-line results from the recent pivotal trial of zanidatamab in BTC and the first overall survival data for zanidatamab from the phase II first-line GEA study. In December, our partner, Zymeworks, announced positive top-line results from a pivotal phase IIb open label single-arm clinical trial called HERIZON-BTC-01. Evaluating zanidatamab as monotherapy in patients with previously treated HER2-amplified and expressing BTC. In the trial, 41% of these patients with HER2-amplified and expressing disease achieved an objective response as assessed by a blinded independent central review. The median duration of response at the time of data cutoff was 12.9 months. By contrast, standard of care chemotherapy in second-line BTC would be expected to have an objective response rate of less than 10%. The safety profile of zanidatamab in the trial was consistent with that observed in previously reported monotherapy studies. Currently, there are no HER2-targeted therapies approved for the treatment of BTC, and we plan to discuss the potential regulatory path forward for zanidatamab in BTC with the FDA. In January, at the ASCO GI Conference, the first overall survival data for zanidatamab were presented from a phase I trial evaluating zanidatamab in combination with chemotherapy in first-line patients with HER2-expressing metastatic GEA. The preliminary results showed that zanidatamab in combination with chemotherapy is a highly active treatment regimen with the ability to generate significant and durable responses. At the time of the analysis, the median overall survival had not yet been reached, with a median duration of study follow-up of 26.5 months. The 18-month overall survival rate was 84%. The overall survival findings in this trial are compelling, given the historically reported overall survival rate for the currently approved standard of care is a median of 14 months. These results show zanidatamab's potential as a foundational treatment for patients with HER2-positive GEA, and we look forward to additional data from the ongoing pivotal phase III GEA trial expected to read out in 2024, which may support U.S. and global regulatory findings. Importantly, ongoing research efforts on zanidatamab will inform development and indications beyond BTC and GEA. Turning to slide 15, we've detailed key clinical programs in our pipeline. Starting with neuroscience, we have initiated a phase I trial for the treatment of Parkinson's disease tremor for JZP385 or suvecaltamide. This is in addition to our ongoing phase IIb trial in essential tremor, for which we anticipate top-line data in the first half of 2024. For JZP150, enrollment is ongoing in our phase II PTSD trial, with top-line data expected later this year. In four Q 2022, we initiated our phase I program for the orexin-2 receptor agonist JZP441. There are currently healthy volunteer trials in the clinic. We anticipate initial proof of concepts in healthy volunteers this year. Moving to oncology, as Dan mentioned, we are continuing to execute a robust development effort for Zepzelca. This includes an ongoing phase III trial in collaboration with Roche to evaluate Zepzelca in combination with TECENTRIQ in first-line extensive stage small cell lung cancer. A confirmatory phase III trial in second line small cell lung cancer being run by our partner, PharmaMar, and our own post-marketing observational trial in second line small cell lung cancer. We are also exploring Zepzelca in other solid tumors in a phase I basket trial. With respect to our supplemental BLA submission for an IV formulation of Rylaze, we have received a complete response letter from the FDA requesting additional clinical data on the IV administration of Rylaze. I want to stress there is no impact on the approved product labeling for Rylaze's intramuscular administration. We are currently evaluating the CRL to determine the next steps. Our marketing authorization application submission for JZP-458 to the European Medicines Agency is currently under review, with potential for approval in 2023. We are also advancing our program in Japan for potential submission, approval, and launch. While not listed on this slide, I'll also note that in October, we initiated our phase I clinical trial for JZP815, our pan-RAF inhibitor for the treatment of solid tumors that have mutations in the MAPK pathway. The pan-RAF inhibitor program is part of a novel class of next-generation precision oncology therapies that has the potential to benefit cancer patients with high unmet needs in multiple different solid tumors. Also, recruitment is expected to begin shortly for our first clinical trial of JZP541, a cannabinoid from the GW platform, assessing its utility in treating irritability associated with autism spectrum disorder in adults. In summary, with the initiation of multiple clinical trials in 2022, we continue to expand our pipeline into disease areas with significant unmet patient needs that provide strong opportunities for long-term sustainable growth. We expect to submit several investigational new drug applications throughout 2023. Increased investment, upcoming catalysts, and expanded capabilities in R&D give us confidence in our ability to deliver sustained long-term value to both patients and shareholders. I will pass the call off to Renée for a financial update. Renée? Thanks, Rob. I'll start with our top-line results on slide 17. As a reminder, our full financial results are available in our press release and 10-K. In 2022, we recorded significant year-over-year revenue growth of 18%, driven by our key products in both neuroscience and oncology. We achieved $3.66 billion in revenues for the year and almost $1 billion in revenues in the fourth quarter. Launching multiple products over the past three years, coupled with the acquisition of GW Pharmaceuticals, has enabled us to successfully diversify our revenues, meeting our 2022 diversification target of 60%-65% of net product sales coming from products launched or acquired since 2019. Given our expectations regarding the durability and growth potential of these products, along with our continued focus on adding new products through corporate development, we believe we are well-positioned to achieve our Vision 2025 goal of $5 billion in revenue. Turning to slide 18, our disciplined capital allocation and focus on operational excellence drove adjusted net income of $934 million, which includes $444 million of IPR&D expense related to corporate development. Contributing to IPR&D were upfront payments for key pipeline additions such as zanidatamab and JZP441, which have the potential to create sustainable long-term value for our company. Our efforts to improve adjusted operating margins to 48% in 2022 have given us additional flexibility to invest in our business and contributed to our significantly enhanced cash generation. In 2022, we generated almost $1.3 billion in cash from operations, an increase of $493 million or 63% compared to 2021. On slide 19, we've highlighted our success in rapidly delevering our balance sheet following the GW transaction. By delevering two full turns since the deal closed in May of 2021, which we accomplished through both debt reduction and enhancing our adjusted EBITDA, we achieved our deleveraging target 6 months ahead of schedule. We exited the year with an adjusted net leverage ratio of 2.9x, which reflects cash outflows of $375 million in the fourth quarter to fund the zanidatamab transaction. Our delevered balance sheet and strong cash flow position us with continued strategic flexibility to invest in our current business as well as corporate development opportunities. Our revenue guidance for 2023, outlined on slide 20, reflects our confidence in the durability of our oxybate franchise and our expectations for continued growth across key products. Our 2023 guidance for neuroscience of $2.675 billion-$2.825 billion encompasses our growth expectations for both Xywav and Epidiolex and the continued decline in Xyrem due to strong Xywav adoption, authorized generics of Xyrem, and potential competition from an additional high-sodium branded oxybate. For simplicity, our neuroscience guidance also includes AG royalties, which will be recognized within total revenues under royalties, not under neuroscience net product sales. Due to the royalty structures within our AG agreements, we expect our royalties to be higher in the second half of 2023 relative to the first half. We remain confident in the durability of our oxybate business, now led by lower sodium Xywav, which is our largest product by net sales and is expected to generate more than $1 billion in net sales in 2023. Our oncology guidance of $950 million-$1.05 billion with a midpoint of $1 billion reflects expectations of continued double-digit growth for this franchise, driven by the expected performance of Rylaze and Zepzelca. Our total revenue guidance range for 2023 is $3.675 billion-$3.875 billion, positioning us for total revenue growth year-over-year. Turning now to OpEx and the bottom line on slide 21. Our SG&A guidance of $1.045 billion-$1.105 billion is a reduction compared to 2022. As we continue to focus on operational excellence and our operating margin, we are gaining greater leverage from our global footprint and commercialization expenses. Our R&D guidance of $675 million-$725 million represents enhanced investment over 2022, reflecting the growth and maturation of our pipeline. In 2023, we'll be investing in a robust pipeline with 23 novel candidates across neuroscience, oncology, and cannabinoids, representing 4 times the number of projects we had in 2015. At the midpoint of our guidance, we'll be investing approximately 19% of revenue into R&D, which is indicative of our continuing transformation. Assumed in this spend are the zanidatamab and Zepzelca clinical programs, later stage trials for suvecaltamide in both essential tremor and Parkinson's disease tremor, JZP150 in PTSD, as well as earlier stage trials for neuroscience programs like JZP441 and oncology programs such as JZP815 and JZP898. As Bruce and Rob noted earlier, we have key value inflection points in 2023 and 2024 that have the potential to create meaningful long-term value. On the bottom line, we expect to continue to deliver strong adjusted net income with 37% growth at the midpoint and a guidance range of $1.24 billion-$1.31 billion. The midpoints of our financial guidance imply an adjusted operating margin of approximately 46% for the year. We'll continue to prioritize commercial, R&D, and business development efforts that we believe will deliver the most value, leveraging our strong cash generation to invest in our business, improve our bottom line, and continue to deliver strong shareholder returns. Looking ahead to 2023, with our strategic investments, expanding product portfolio, R&D progress, and focus on operational excellence, we believe we are well-positioned to achieve Vision 2025 and deliver further diversification, sustainable growth, and enhanced value to patients and shareholders. I'd now like to turn the call back to Bruce. Thanks, Renée. I'll conclude our prepared remarks on slide 23. 2022 was a transformative year for us. We achieved strong double-digit revenue growth and improved our operating margin significantly. Our commercial teams demonstrated strong performance across our portfolio. We're confident that Xywav will remain the oxybate of choice in 2023, entering the year with blockbuster status. We expect growth for Epidiolex and that our oncology franchise will continue to deliver. Our R&D organization has reached new levels of productivity and expanded its capabilities. We added three new molecules in 2022 and have trials for multiple products underway, ranging from potentially pivotal trials to early-stage studies. We are employing greater discipline in our capital allocation strategy, which is aimed at the highest priority areas, including R&D programs and corporate development. With our strong cash flow, balance sheet, and adjusted operating margins, we have the flexibility to make significant investments across commercial, R&D, and corporate development to drive sustainable growth and enhanced value. We're excited about building on our current momentum in 2023 and expect growth across our key products. Vision 2025 provides a clear perspective on what we expect to achieve in the coming years. We're excited about the future and what we can deliver to patients and shareholders. I look forward to updating you on our progress as we advance. That concludes our prepared remarks. I'd now like to turn the call over to the operator to open the line for Q&A. Thank you. If you'd like to ask a question, please press star one one. If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from Jessica Fye with JPMorgan. Your line is open. Great. Thanks so much for taking the questions. Ideally two, if you can. First, can you talk about how Xyrem dynamics are playing out relative to your expectations since the authorized generic entered? Second, understanding you're no longer guiding by product franchise here, can you speak a bit to your expectations for Epidiolex growth? Is it possible that growth for that business accelerates in 2023 relative to 2022 with just increasing ability to be in the office, et cetera? Thank you. Thanks, Jess. On your question about Xyrem, let me first just put this in context. You know, our major focus for 2023 and going forward is growing Xywav. You know, both in narcolepsy and idiopathic hypersomnia. That's been our focus. We've had competition for Xyrem for the past couple years. It's been us with Xywav, and we've seen Xyrem sales coming down. As to what we're seeing with the AG, maybe I'll ask Kim to give a couple thoughts on our experience thus far in 23, although we're obviously not reporting first quarter results right here. Maybe Kim, you could just transition right into Epidiolex growth and dynamics there. Sure, Bruce. Happy to do that. You know, as Bruce said, it's really too early here. We're in the early stages. It's a comment on the overall impact of the AG, you know, on Xyrem. As he said, our focus does remain on Xywav. You know, we're feeling that we're gonna continue to expect in 2023 continued strong uptake of Xywav in both narcolepsy and IH, with continuing transition of narcolepsy patients from high sodium oxybates, either that be the Xyrem or later on, from the AG over to Xywav based on its differentiation as the only lower sodium oxybate product. As a result, we also continue to expect that Xywav will both grow and remain the oxybate choice in 2023, even with one or more authorized generics on the market and potentially branded competition entering later on in the year. You know, overall, you know, our guidance includes continued decline in Xyrem, both due to strong Xywav adoption and the AG entry and potential competition. We feel very optimistic about the ability of Xywav to continue to grow through 2023. In terms of Epidiolex and the question about whether or not it can accelerate, what I'll basically say is that we're continuing to be very pleased with the Epidiolex net product sales that it increased 12% on a pro forma basis in 2022 compared to 2021, and that we're very pleased that this has been driven primarily by demand. We're continuing to add new prescribers still to our active prescriber base. Our overall engagement, as Dan said, of HCPs continues to grow, which is really positive for this product in a very promotionally sensitive market. Dan also mentioned the driver of 60% of prescribers now indicating to us that they're using Epidiolex even earlier in the treatment algorithm. Heading into 2023, you know, we're, we've got, a new push in terms of, you know, payer coverage. You know, we've talked for several years about the payer coverage, being quite strong, you know, from a quantitative standpoint for patients. We're really pleased that, you know, our contract tracking efforts in last year really has paid off and that we're entering 2023 in an even stronger position with payers. We've seen several plans, reduce at the start of 2023, their utilization management criteria, ultimately making it, a bit easier, for HCPs and, patients to get, access to Epidiolex. Then we're gonna continue, to, you know, promote the synergistic effect of using Epidiolex in combination with clobazam. You know, we've been out there doing that for a year, but HCPs are continuing, you know, to have a very impressed reaction to these data that have shown that we can reduce seizures by around 60% in LGS and Dravet, and nearly 50% in TSC. Overall, we're very excited about the future potential of Epidiolex as a significant contributor to our top line and to Vision 2025. Thank you. Ladies and gentlemen, we ask that you please limit yourselves to one question. Our next question comes from Marc Goodman with SVB Leerink. Your line is open. Yes. Can you give us a flavor for the persistence of these patients, the IH patients, and how that's going? We know what the number is at the end of the quarter. I'm just kind of curious if, you know, if there are a lot of patients that are already dropping off and you're getting a lot of new patients, so that's the net effect. Just trying to get a sense of that. Maybe on an absolute basis, you can give us a sense or even on a relative basis, relative to how the drug is used for narcolepsy and the persistence there. Just maybe give us a sense there. Then just one quick question just on the R&D guidance. Is there included any, like, major milestones in there, or is that just increased because of the clinical studies that you've already mentioned? Maybe, Kim, we'll come to you on what we're seeing in terms of patients staying on IH, thus far in launch, although we're still pretty early. Renée, maybe you can take the question on R&D guidance. Kim? Got it. Had to come back off of mute. Yeah, so we're 14 months into the launch, you know, we continue to be really pleased with the uptake. We're still seeing from the marketplace a lot of excitement about having the first and only approved product for IH. You know, we have had compelling growth continue into this quarter with 1,750 active patients exiting the quarter, and we're expecting to have continue to have a strong growth here. In terms of persistence, I basically just say it's pretty consistent in terms of what we see in narcolepsy. The number we do report around active patients is that net number that includes both those coming on and as well as those coming off. You know, our focus in IH, you know, remains on educating prescribers on how to better diagnose IH and identify patients who would benefit from Xywav. You know, we're reminding them that IH is a 24-hour condition and that Xywav is approved to treat the full condition and can address multiple symptoms of IH, not just the daytime symptom of excessive daytime sleepiness. You know, keep in mind, I think we cautioned for some while that, you know, we're building the market here. This is the first and only FDA-approved treatment for IH in adults. You know, overall, in the long term, we feel as we build this market, we're really confident in our ability to ultimately maximize Xywav's potential in this, you know, very underserved marketplace. Yeah. I'll just chime in, Marc, with respect to the R&D milestones. Our increased R&D guidance is really a reflection of an expanded, more robust pipeline. Clearly you saw the expenses in Q4 come up, a reflection. Taking on the zanidatamab program, which we want to invest fully behind across 2023. It's a combination of zani and the clinical programs to support that, the later-stage studies for suvecaltamide, of course, JZP150 we expect to read out at the end of this year, and then the broader expansion altogether. I had mentioned on the call that, you know, we have a pipeline today that's four times the size of the one that we had not that long ago in 2015. The focus we've had on disciplined capital allocation has enabled us to be able to lean more into R&D as part of our spending in 2023. Thank you. Our next question comes from Jason Gerberry of Bank of America. Your line is open. Hey, guys. Thanks for taking my question. My question pertains to your sales guidance for 2023. It, it looks pretty conservative, especially in the context of Vision 2025, which ex corp development, I think, is $4.5 billion, which would imply, like, basically, off your 2023 midpoint, you have to gain $350 million in sales in 2024 and 2025 respectively, but you're only modeling about + $100 million in revs in 2023. Just wondering if you could shed a little bit more light on that dynamic, that would be helpful. Thanks. Yeah. Thanks, Jason. I'll start and then invite Renée to jump in. You know, what you're seeing in 2023, and I think Renée did a nice job of this in laying out the guidance, is real growth in all of our core products offset by a continuing significant decline in Xyrem. I just think as you get out to later years, you're gonna continue to see growth in our key products, but you've already suffered a lot of the loss in Xyrem, and so the net gain becomes a little clearer. I think one of the rationales of rolling out Vision 2025, to give people a little more context of growth curve over time was to make sure people understood that we would be going through this transition in 2023. Yeah. Maybe just to build on that further, Bruce. You know, as Bruce described, we had, you know, we have these multiple dynamics at play, right? We have this dynamic of growth within Xywav, Epidiolex, Rylaze, and Zepzelca, but that is offset by this continued decline in Xyrem, in large part due to the strong uptake of Xywav, but also through the introduction of AGs, which of course we earn royalties on. As we, you know, move forward, we also expect, as Bruce had mentioned, to see continued growth in 2024 and 2025. What does it mean based on our 2023 guidance, which does have more muted growth on a consolidated basis based on the dynamics that we've shared here today? What does it mean in terms of 2024 and 2025? Well, that means you're delivering low double-digit growth from your existing business and continuing to be active on the BD front, which we expect to be. We've also stated that we do expect zani to contribute to our 2025 revenue. We also expect we'll need to continue to be active as we have been over the last several years, each year closing, a transaction that has, resulted quite quickly in revenue generation. That's how we're thinking about the overall guidance, and feeling good about where we are. Thank you. Our next question comes from Annabel Samimy with Stifel. Your line is open. Hi. Thanks for taking my question. I'm gonna be different and ask something about your new product, this pipeline product, zani. Regarding the phase II open label data, in first-line GEA in combination with chemo, I guess, can you put this into context with the current phase III data or phase III trial that's ongoing, and how comfortable are you that I guess some of this data can be indicative of potential success in the in the phase III study? How similar are the different arms, and is there something that you can draw from it, or is the population too small at this point? When might we be able to see this data? Then just as a quick follow-on, you clearly have a number, a tremendous number of opportunities here with anti-HER2 agent. How will you be making the decisions on the new tumor types, and when might we be able to hear about some of these programs that you're gonna be moving forward? What gets you excited? Thanks. Annabel. Rob loves it when you say what gets him excited about our pipeline. on zani, you know, we're in the really fortunate position of having had a couple data readouts even since we signed the initial transaction that give us confidence. I'll let Rob jump in on specific answers to your questions. Yeah. Thanks for the question. Thanks, Bruce. You have it right. I described the very strong data from the single-arm phase two trial that's frontline zanidatamab in combination with standard of care. That was meant to provide data, you know, in support of the ongoing pivotal program. I think the results give us a lot of reassurance about what we can expect in that phase III pivotal program and confidence that it's likely to be the standard of care. You're thinking about that in the right way In terms of where else to go with this, if you look at all the data published now, BTC, gastric, breast cancer data, other data from the phase I trial, it's very clear that this is a highly active anti-HER2 therapy in just about any tumor type that is overexpressing HER2. In fact, we see activity in patients progressed on other anti-HER2 therapies, which is very important as you think about where to position this next in different different lines of therapy. We're actively looking at different opportunities beyond our current strategy. As you know, we're planning a faster market strategy with BTC, and then our next pivotal trial in gastric, but looking at other opportunities. Thank you. Our next question comes from David Amsellem with Piper Sandler. Your line is open. Hey, thanks. I wanna switch gears to one of your pipeline products. This is the orexin agonist JZP441. In the study, if I'm not mistaken, you're dosing it at nighttime. I'm just trying to get a better sense as to the rationale here, given that this is a ostensibly a wakefulness or alertness drug. Do you think that there's something there that could set you apart from the other orexins that are in development, be it the Takeda one or the one from Alkermes or potentially others? Thank you. Yeah. Rob, do you wanna jump in on that? Yeah, happy to. Of course. I'll answer the second part first, which is, you know, we looked at this molecule carefully before we did the deal, preclinical data, emerging clinical data. We do have a lot of confidence around it being differentiated potentially to other products that are in development. In terms of our approach to the study design, you asked specifically about dosing healthy volunteers at night. This is really a way for us to quickly, in healthy volunteers, establish establish the proof of concept around wake promotion. In healthy volunteers, when they're sleep deprived, you can then measure alerting effects in that population that would be harder to measure in, you know, during the daytime in an otherwise healthy population. As we do that rising single dose study, evaluating increasingly higher doses, we then have an opportunity to interrogate the relative wake promoting effects across those doses, which then sets us up for the necessary downstream studies. Clearly then we need multiple dose safety, and that will help us select the dose for the study that we just posted on clinicaltrials.gov, and then ultimately together, help us to select the dose for the first patient studies. Thank you. Our next question comes from Gary Nachman with BMO. Your line is open. Thanks. My question's on Rylaze, which has been growing pretty nicely. How much will the Monday, Wednesday, Friday dosing help further uptake of that product? What's the cadence for expanding Rylaze geographically, including the EU and Japan? How much will those ex-U.S. markets ultimately contribute? With the CRL for the IV, how important is that ultimately to the franchise? Would there be a long-term impact if you don't move forward with it? I know there won't be an impact in the near term, but what about the long term? Thank you. Thanks, Gary. I'm gonna reorder your questions a little bit, maybe have Kim take Monday, Wednesday, Friday dosing and then comment on any impact of not having IV. Dan, maybe you can take the ex-U.S. piece of this. Kim? Great. Thanks for asking about Rylaze. You know, we're really pleased that the sales for Rylaze, you know, have exceeded the prior U.S. peak sales with Erwinaze. We believe this is a really strong signal that, you know, the unmet needs of the market had never, you know, truly been satisfied. In, in terms of Monday, Wednesday, Friday dosing, you know, we really believe when we put this out there that our customers were utilizing Rylaze and not denying any patients, you know, access to it because we had a label with every 48-hour dosing. We really were not expecting a lift in sales from the Monday, Wednesday, Friday dosing, but instead, you know, probably a lift in customer satisfaction in terms of customers who are used to, and this is the preferred, you know, route of way of dosing the product, would, you know, be able to administer it in a way that, you know, was closer what they're historically used to and prefer. Just following up on Kim, this is Dan. Very quickly on the CRL question, we don't see that as a limitation to the uptake in the U.S. market. We're just looking to get that additional data in the hands of the HCPs, ideally through the label, but it's also been published and presented at ASH. The IM uptake has gone very well. Outside the U.S., we filed with the EMA last year, and we do anticipate a, you know, approval coming sometime. I can't remember. You guys can let me know if we've given the specific timing. On the Japan side, we are gonna be engaging with the health authorities and trying to bring this program, you know, differentiated from Erwinaze to the marketplace. There's still no non-E. coli based Erwinia in the Japanese market. In terms of overall growth, it really depends a little bit on pricing. You know, Europe and the U.S. and Japan likely would be more tied to a lower pricing. Historically we saw, you know, 80% of Erwinaze revenue coming from the U.S. versus Europe, while there's still a lot of patients over there. Ultimately it depends on how we can differentiate the product. You know, near term focus, of course, is getting the product approved. The EU potential for approval is later this year. Thank you. Our next question comes from Balaji Prasad with Barclays. Your line is open. Thanks for the questions. Just two from me. Firstly, with Vision 2025, including around $2 billion of oxybate, would you discuss the relative role or contribution between narcolepsy and IH towards this vision? Secondly, with Epidiolex, I wanted to address a point where we're getting significant investor questions, which is the generic challenges to Epidiolex with 10-11 filers. Is there any confidence that you can provide the market around the durability of Epidiolex? Just want to see that ensure that there's not an overhang on the stock for the longer run. Thanks. Maybe I'll take that second question first, and then we can have maybe Renée jump in a little bit on what we've said in terms of the oxybate revenue piece of Vision 2025. Epidiolex, there's no new information out there on durability. We've said from the time we first announced the GW transaction that we did have a lot of confidence in the durability of this asset. We had predicted correctly the likely timing of first ANDA submissions, and of course, that's public now with our announcement of the Hatch-Waxman litigation. You know, since the time of the deal, we did have additional IP issue, including some with longer duration patents. That's not a surprise. We had again predicted that at the time of the transaction. You know, I don't have new information to share other than all the things we've shared historically that give us confidence that this is not, a short duration, product. Yeah. Balaji, on your other question. Renée. Yeah, I was just gonna ask kim to jump in there. Yeah, sure. I think your question was about, you know, what we see the long term mix being between narcolepsy and IH for Xywav. You know, overall we see it as a very durable franchise, and, you know, we do expect Xywav to provide substantial value in both the near and the long term. We expect that Xywav will both grow and remain the oxybate of choice in 2023. In addition to this, IH is a very meaningful growth opportunity as the only FDA approved treatment for IH. It's really a combination of the two, contributing very meaningfully moving forward. Maybe I'll just jump in quickly then on the royalties. I think that may have been an aspect of your question as well. I'd mentioned during the prepared remarks that with respect to the royalties on authorized generics of Xyrem, you should think about those being higher in the second half versus the first half of the year. Recall the way that the royalties work. The first six months, we just have Hikma on the market, and we have tiered wide-ranging royalties, which are essentially low, where they are selling a low percentage of the overall oxybate volumes, and then those increase as those volumes increase. That royalty rate ranges from 10 all the way up to 90%. Recall they're exclusive. The second 6 months of this year, we expect the royalties to be higher because the royalty rate with Hikma increases to a fixed rate where both we and Hikma have substantial economics. Then we have the expectation of three other extremely volume limited AGs coming in with low fixed rate volumes and royalties to Jazz. As we go forward, recall that after the first year, then the royalties with Hikma exceed, sorry, accelerate to a much higher double-digit rate to Jazz and remain at that through the duration of the royalty period. Th ank you. Our next question comes from Gregory Renza with RBC. Your line is open. Great, thanks. Hey, Bruce and team. Thanks for taking my question. Maybe Bruce, just one for me. How is the current commercial performance across your products and segments really feeding back to the early pipeline selection that, you, Rob, and the team are doing the no-go decisions there and the risk tolerance? Just maybe thinking about the commercial products, how that actually is affecting or influencing what you see as diversification of the portfolio. Of course, as Renée mentioned, with the pipeline being 4 times the size now, are there particular areas where you'd like to see greater pipeline output from? Thanks so much. Yeah, love the question. you know, I would say that we keep learning the same lesson over and over, which is if you have great products that really meet an unmet patient need that are differentiated from other products, those continue to have high value in the marketplace and get preferentially adopted. I think the ways in which Xywav and Epidiolex and Rylaze and Zepzelca have all filled unique needs and are differentiated from other products has made a big difference in their success thus far and their future success. I would say the same thing about the programs we have in the pipeline. We think the ones we're investing most heavily in, particularly in later stage where we have more data, fall into that category of meet significant unmet patient need and are differentiated from other currently available or expected to be available therapies. You know, in the earlier part of the pipeline, we're taking some bigger risks and shooting for some, you know, big targets. Some of those will work and some of those won't. We don't know which ones are which yet. But we're gonna ride the winners, and the winners are gonna be those ones that are highly differentiated. Dan, I wanna give you a chance to weigh in here too, if you'd like to add anything in particular about the translation of our commercial experience back to R&D choices. Yeah. Thanks, Bruce. I mean, one thing to take in mind is, you know, some of our pipeline is also evidence generation, new indications, new formulations of our existing brands. We wanna continue to unlock the full potential of those brands, including broadly Epidiolex and Oxybate and even on the oncology side. I mean, zani is a pipeline within a product, of course. How we kinda think that through and where we can get the most differentiation and, you know, PTRSs, et cetera. It's a great set of challenges that we've got with the pipeline and the commercial portfolio. Clearly, remaining and enhancing our category leadership and now epilepsy, sleep medicine and increasingly some of these areas in both solid and liquid tumors is also, you know, an incentive for the way we think about building out the pipeline. We have, you know, under Rob's leadership, really created much more internal capability all the way from filing our own INDs through development to also a corporate development muscle, which I'd say is second to none, where we can really look at external innovation. Folks are knocking on our door because of the success we've done in some of these partnerships, whether late stage or early, pipeline. It's a good place to be. We will move into some new areas, as Bruce referenced, where there's significant unmet need, and we think we can get to some smart go, no-go, decision points. Thank you. Our next question comes from Brandon Folkes with Cantor Fitzgerald. Your line is open. Hi. Thanks for taking my question. Maybe just one on Zepzelca. Any updates on the enrollment and timeline expectations for LAGOON and IMforte? Any chance of getting the potential first line move complete, or before or during 2025, just as you think about Vision 2025? Thank you. Rob, you wanna talk about Zepzelca, clinical trial, expectations? I would maybe ask just for a reminder from our group in terms of what's been communicated previously, but I would just say that that trial is on track relative to expectations, and we really are quite excited about the potential to have Zepzelca move up into the front line, where we're preemptively treating patients before they progress, accessing more patients, treating patients for a longer duration of time. Thank you. I'm seeing now that what we had said previously that we're expecting the complete enrollment this year. In the first line trial. Yes. Thank you. Our next question comes from Ash Verma with UBS. Your line is open. Hi. thanks for taking question, my question. I have two. first one on suvecaltamide. What's the level of confidence here in the essential tremor mechanism, the T-type calcium channel pathway? We've seen that Neurocrine failed with the same mechanism and practice data as expected shortly. Is your molecule in any way different versus some of these competitors? second, I wanted to see if you can provide any kind of a color on what you're observing in the marketplace for the Xyrem AG. Are stable patients getting switched to AG whenever they're going back to the physicians for their regular checkup? Or are the insurance plans driving the AG uptake without patients seeing the doctor? Trying to just get a sense of how quickly Hikma can take a share here. Let's go first to Rob on the, on the 385 question, on the suvecaltamide question. Yeah, I would start just by saying that we had the benefit of a phase Ia proof of concept study before initiating our current trial, which enabled us to see that in fact, there was the response that we expected to see based on the mechanism and consistent with our preclinical data. It also allowed us to identify what would ultimately be the right patient selection criteria and the right endpoints, of course, in agreement with the FDA, for that trial. We think the prior data that we had in our phase I with our molecule gives us confidence about the outcome of the ongoing phase Ib, which as you know, is three doses with a once daily formulation. Yeah. I'll just add on the second part of your question, probably too early for us to comment on payer dynamics. You know, we saw obviously where Hikma put their WAC pricing at the time of launch. You know, we're aware that there is some uptake of the AG as we would expect and as was built into our expectations coming into the year and as is built into the guidance we've given you. I don't think we've got enough data yet to get more specific. Thank you. Our next question comes from Ami Fadia with Needham & Company. Your line is open. Great. Thanks for taking my question. Maybe firstly, just on the IH market, since you've been, you know, in the market for some time now, any sort of updated thoughts around the size of the market and the value of Xywav? Are you seeing more patients being diagnosed and treated in the market? And then, just to follow up on JZP385, can you remind us how you're thinking about the essential tremor patient population as opposed to the Parkinson's disease? Are there similarities or differences that we should be thinking about, as we consider, you know, if, if we see positive data of in essential tremor, do we, you know, does that give us greater confidence that the Parkinson's disease trials would also work? Thank you. Kim, maybe you could start on just how you're thinking about the IH opportunity overall. Yeah, sure. You know, I'll start, you know, by reiterating that we feel like we have compelling growth in IH, you know, already with 1,750 patients coming out of the end of the year and do expect it to grow nicely moving forward. You know, as we've said, you know, we are, you know, building a market here. There's quite a bit of education to do. You know, we're still trying to estimate ultimately how big this will be. We feel very optimistic, but we know we need to still educate prescribers on how to better diagnose IH. There are 37,000 patients out there we've been talking about that are diagnosed and actively seeking treatment. You know, the HCPs have kinda shown us that they tend to think fairly narrowly about the condition as being all about excessive daytime sleepiness. We're reminding them, you know, that this is a 24-hour condition and that, you know, we're approved with Xywav to treat the full condition and address multiple symptoms of IH, not just EDS. Again, this is the first and only approved treatment that prescribers really haven't had to think much more beyond EDS so far to date. We really, you know, feel good about the way that they're coming along and starting patients and we're confident in our ability to ultimately, you know, maximize the opportunity, you know, of the product in this really underserved market. Dan, do you wanna jump in on the JZP385's two different market opportunities? Dan, are you on mute? I was on mute, Bruce. Thank you. Yeah. Sorry. On sort of ET and Parkinson's, I mean, what's similar to it is, you know, a significant unmet need. ET, there's been no, you know, new approved therapies and the therapies that are there have very little limitations. No approved therapy in 50 years, nothing approved for Parkinson's tremor. We do think there's overlapping pathophysiology between the tremor types though, and there is some preclinical, you know, opportunity for us to as well think that T-type calcium channel blockers should work there. In terms of the market opportunity, it's, you know, 2 million have diagnosed across the Western markets. We think the actual market opportunity for essential tremor is up to 11 million. It's that classic, you know, with the right drug, you can really uncover a lot of market growth and opportunity. On Parkinson's, you know, that's a more defined patient population and, you know, very addressable in terms of Parkinson treating physicians. It's about 1 million, you know, patients per year of which 75% have tremors for which there's no approved therapy. Exactly how we would configure the sales force if we're lucky enough to get both indications is something we'll be figuring out. We do think from a price value as well as, you know, market coverage and interest from both HCPs and patients, it could be quite a large market. Thank you. Our next question comes from Madhu Kumar with Goldman Sachs. Your line is open. Good afternoon. This is Omari on for Madhu. Our first question is how should we think about the ex-U.S. launch of Epidiolex in Europe as a mic for future growth? How should we think about potential opportunities for corporate development? You mentioned you all be open to seeking new areas. Would these be still within the core of oncology or, and neuroscience, or could you expand outside of that? Okay. Let's I'm in a minute gonna come to Dan on ex-US Epidiolex opportunity and then Renée on corporate development. Before that, I think there might have been a dangling part of the last question we didn't get, which was really how to think about the two clinical trial populations and whether there's any relationship, and how to think about potential results in essential tremor as they might apply to Parkinson's tremors. Rob, maybe you could jump in on that first. Thanks, Bruce, and I do think Dan covered it, with respect to, yes, these are two distinct clinical entities. We have strong preclinical rationale that the mechanism of T-type calcium channel inhibitors could help block the tremor associated with each of these conditions. While certainly, you know, if we see a sort of readout in either of these indications, it's gonna give us increasing confidence around this molecule, in working the way we think it should work. I wouldn't have a direct read-through, you know, to say if it doesn't work in one, it won't work in the other. On the ex-US growth for Epidiolex, we do see strong continued growth for in 2023 and contributing toward 2025. Importantly, we had some headwinds that we don't think we'll face as directly in terms of FX rates. Importantly now we've got approval toward the end of last year in France with full reimbursement, so we're now fully launched in all five major European countries. We've still got some smaller markets to add over time. You know, we're launched in 15 of 35 approved markets. More from a medium-term perspective, we see significant opportunity in the Asia Pac region, and in particular Japan, where we've got a phase III study ongoing and we look forward to, you know, thinking through our commercialization strategies there for the neuroscience portfolio. Maybe just jumping in on corporate development. In terms of areas we're interested in, clearly we're definitely focusing on neuro and oncology, but we're also looking more broadly at rare and orphan in general. This is a space that we're very comfortable in, currently within our neuroscience and oncology therapeutic areas. As we're looking at corporate development opportunities, we've tended to be technology agnostic, meaning between small molecule, large molecule, botanicals. As we continue to build, enhance our commercial capabilities, Bruce had mentioned earlier this strong focus on patient need when you can have a meaningful impact for patients to be able to apply our insights. It gives us confidence in looking at multiple types of molecules and potentially extending beyond neuro and oncology. The primary focus is still in our neuroscience and oncology therapeutic areas. In terms of the stage of compounds, we're looking at commercial, near commercial, but also pipeline deals. You've heard us talk about our guidance today. We're investing heavily there. We do think our increased capabilities that we've developed both organically but also with the acquisition of GW have set us up really well. Thank you. Our last question comes from Greg Fraser with Truist. Your line is open. Great. Thanks for squeezing me in. On Xywav, you're clearly confident in continued strong growth for both indications. On narcolepsy, do you expect the pace of new patient adds to potentially slow a bit this year given the oxybate market dynamics? Last year, I think you added about 500 new patients each quarter. Curious as whether you think that pace could continue with the various moving parts in the oxybate market this year. Thanks so much. Kim, anything you wanna add on narcolepsy adds in 2023? Just that, you know, we're still confident here that we've got clear differentiation, you know, based on the reduced sodium, and that we're gonna continue with a nice pace, both in terms of patient conversions, as well as new patient starts, where we're just already seeing the vast majority of patients, being started on Xywav versus Xyrem. You know, overall we feel really good about that momentum continuing throughout the year. Thank you. There are no further questions. I'd like to turn the call back over to Bruce for any closing remarks. All right. Thank you, operator. I just... I wanna close by recognizing the passion and innovation of our 2,800 talented employees around the globe who come to work each day dedicating to improving the lives of more patients than before. I also wanna thank our partners and our shareholders for their continued confidence and support. Thanks everyone for joining us today, and stay well. Thank you for your participation. You may now disconnect. Everyone, have a great day.